The Vehicle of Administration and Prandial State May Reduce the Spectrum of Oral Broad-Spectrum Antibiotics (Oxytetracycline, Fosfomycin and Amoxicillin) Administered to Piglets: A Pharmacokinetic/Pharmacodynamic Approach.

The objective of this study was to assess the impact of the vehicle of administration and the prandial state of post weaning piglets on the indices of therapeutic efficacy for different broad-spectrum antibiotic/pathogen combinations. Pharmacokinetic data were retrieved from previous studies, in which we orally administered oxytetracycline (OTC), fosfomycin (FOS), or amoxicillin (AMX) according to the following treatments: dissolved in soft water to fasted or non-fasted piglets, dissolved in hard water to fasted or non-fasted piglets, and mixed with feed. Minimum inhibitory concentration (MIC) values for susceptible strains of bacteria causing swine diseases were obtained from the database of European Committee on Antimicrobial Susceptibility Testing (EUCAST) for each antibiotic. Pharmacokinetic/pharmacodynamic (PK/PD) indices of therapeutic efficacy-drug exposure over the dosing interval (fAUC/MIC) for OTC and FOS; time that free drug concentration remains above MIC (%fT>MIC) for AMX-were calculated for each antibiotic/pathogen combination under each treatment. After all OTC and in-feed FOS and AMX treatments, the indices of therapeutic efficacy were below the target value for all the study microorganisms. When FOS or AMX were delivered dissolved in soft or hard water, the indices were above the target value over which therapeutic efficacy would be expected for Escherichia coli treated with FOS and, Glaesserella parasuis, Pasteurella multocida, and Actinobacillus pleuropneumoniae treated with AMX. The prandial state of piglets showed no influence on the indices of therapeutic efficacy. Pharmacokinetic profiles of broad-spectrum antibiotics, specifically the ability to achieve target concentrations, may be largely reduced due to drug interactions with components present in feed or water resulting in a discrepancy with PK/PD principles of prudent and responsible use of antibiotics.

Antimicrobial Activity of Bacillus amyloliquefaciens BS4 against Gram-Negative Pathogenic Bacteria.

Worldwide, bacterial resistance is one of the most severe public health problems. Currently, the failure of antibiotics to counteract superbugs highlights the need to search for new molecules with antimicrobial potential to combat them. The objective of this research was to evaluate the antimicrobial activity of Bacillus amyloliquefaciens BS4 against Gram-negative bacteria. Thirty yeasts and thirty-two Bacillus isolates were tested following the agar well-diffusion method. Four Bacillus sp. strains (BS3, BS4, BS17, and BS21) showed antagonistic activity against E. coli ATCC 25922 using bacterial culture (BC) and the cell-free supernatant (CFS), where the BS4 strain stood out, showing inhibitory values of 20.50 ± 0.70 mm and 19.67 ± 0.58 mm for BC and CFS, respectively. The Bacillus sp. BS4 strain can produce antioxidant, non-hemolytic, and antimicrobial metabolites that exhibit activity against several microorganisms such as Salmonella enterica, Klebsiella pneumoniae, Shigella flexneri, Enterobacter aerogenes, Proteus vulgaris, Yersinia enterocolitica, Serratia marcescens, Aeromonas sp., Pseudomonas aeruginosa, Candida albicans, and Candida tropicalis. According to the characterization of the supernatant, the metabolites could be proteinaceous. The production of these metabolites is influenced by carbon and nitrogen sources. The most suitable medium to produce antimicrobial metabolites was TSB broth. The one-factor-at-a-time method was used to standardize parameters such as pH, agitation, temperature, carbon source, nitrogen source, and salts, resulting in the best conditions of pH 7, 150 rpm, 28 °C, starch (2.5 g/L), tryptone (20 g/L), and magnesium sulfate (0.2 g/L), respectively. Moreover, the co-culture was an excellent strategy to improve antimicrobial activity, achieving maximum antimicrobial activity with an inhibition zone of 21.85 ± 1.03 mm. These findings position the Bacillus amyloliquefaciens BS4 strain as a promising candidate for producing bioactive molecules with potential applications in human health.

Repositioning FDA-Approved Drug Against Chagas Disease and Cutaneous Leishmaniosis by Structure-Based Virtual Screening.

BACKGROUND: Chagas disease and cutaneous leishmaniasis, two parasitic diseases caused by Trypanosoma cruzi (T. cruzi) and Leishmania mexicana (L. mexicana), respectively, have a major global impact. Current pharmacological treatments for these diseases are limited and can cause severe side effects; thus, there is a need for new antiprotozoal drugs. METHODS: Using molecular docking, this work describes a structure-based virtual screening of an FDA-approved drug library against Trypanosoma cruzi and Leishmania mexicana glycolytic enzyme triosephosphate isomerase (TIM), which is highly conserved in these parasites. The selected compounds with potential dual inhibitory activity were tested in vitro to confirm their biological activity. RESULTS: The study showed that five compounds: nilotinib, chlorhexidine, protriptyline, cyproheptadine, and montelukast, were more active against T. cruzi, than the reference drugs, nifurtimox and benznidazole while chlorhexidine and protriptyline were the most active against L. mexicana. CONCLUSIONS: The analysis of these compounds and their structural characteristics may provide the basis for the development of new antiprotozoal agents.

Broad-Spectrum Antiviral Effect of Cannabidiol Against Enveloped and Nonenveloped Viruses.

Introduction: Cannabidiol (CBD), the main non-psychoactive cannabinoid of the Cannabis sativa plant, is a powerful antioxidant compound that in recent years has increased interest due to causes effects in a wide range of biological functions. Zika virus (ZIKV) is a virus transmitted mainly by the Aedes aegypti mosquitoes, which causes neurological diseases, such as microcephaly and Guillain-Barre syndrome. Although the frequency of viral outbreaks has increased recently, no vaccinations or particular chemotherapeutic treatments are available for ZIKV infection. Objectives: The major aim of this study was to explore the in vitro antiviral activity of CBD against ZIKV, expanding also to other dissimilar viruses. Materials and Methods: Cell cultures were infected with enveloped and nonenveloped viruses and treated with non-cytotoxic concentrations of CBD and then, viral titers were determined. Additionally, the mechanism of action of the compound during ZIKV in vitro infections was studied. To study the possible immunomodulatory role of CBD, infected and uninfected Huh-7 cells were exposed to 10 µM CBD during 48 h and levels of interleukins 6 and 8 and interferon-beta (IFN-ß) expression levels were measured. On the other hand, the effect of CBD on cellular membranes was studied. For this, an immunofluorescence assay was performed, in which cell membranes were labeled with wheat germ agglutinin. Finally, intracellular cholesterol levels were measured. Results: CBD exhibited a potent antiviral activity against all the tested viruses in different cell lines with half maximal effective concentration values (CE50) ranging from 0.87 to 8.55 µM. Regarding the immunomodulatory effect of CBD during ZIKV in vitro infections, CBD-treated cells exhibited significantly IFN-ß increased levels, meanwhile, interleukins 6 and 8 were not induced. Furthermore, it was determined that CBD affects cellular membranes due to the higher fluorescence intensity that was observed in CBD-treated cells and lowers intracellular cholesterol levels, thus affecting the multiplication of ZIKV and other viruses. Conclusions: It was demonstrated that CBD inhibits structurally dissimilar viruses, suggesting that this phytochemical has broad-spectrum antiviral effect, representing a valuable alternative in emergency situations during viral outbreaks, like the one caused by severe acute respiratory syndrome coronavirus 2 in 2020.

Development, validation and analysis of a human profurin 3D model using comparative modeling and molecular dynamics simulations.

The emergence of new viruses can lead to the outbreak of pandemics as occurred at the end of 2019 with the coronavirus disease (or COVID-19). The fastest way to effectively control viral infections is to develop broad-spectrum antivirals that can fight at least an entire class of viruses. Profurin, the furin precursor propeptide, is responsible for the autoactivation step which is crucial for the maturation of several viral substrates. This role makes the study of furin and profurin interactions interesting for the development of new potential broad-spectrum antivirals for the treatment against several human viral diseases. Since there is no 3D model of profurin published in the literature or deposited in a database, this work reports the development, validation and analysis of a profurin 3D model using comparative modeling and molecular dynamics. The model is available in ModelArchive at https://www.modelarchive.org/doi/10.5452/ma-ct8l7. The usage of this model will make possible further studies of molecular docking and MD simulations of the profurin-furin system, in the design of new potential broad-spectrum antivirals for the treatment against several human viral diseases.Communicated by Ramaswamy H. Sarma.

The Flavonoid Cyanidin Shows Immunomodulatory and Broad-Spectrum Antiviral Properties, Including SARS-CoV-2.

New antiviral treatments are needed to deal with the unpredictable emergence of viruses. Furthermore, vaccines and antivirals are only available for just a few viral infections, and antiviral drug resistance is an increasing concern. Cyanidin (a natural product also called A18), a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, through its anti-inflammatory effects. Regarding its mechanism of action, A18 was identified as an IL-17A inhibitor, resulting in the attenuation of IL-17A signaling and associated diseases in mice. Importantly, A18 also inhibits the NF-κB signaling pathway in different cell types and conditions in vitro and in vivo. In this study, we report that A18 restricts RSV, HSV-1, canine coronavirus, and SARS-CoV-2 multiplication, indicating a broad-spectrum antiviral activity. We also found that A18 can control cytokine and NF-κB induction in RSV-infected cells independently of its antiviral activity. Furthermore, in mice infected with RSV, A18 not only significantly reduces viral titers in the lungs, but also diminishes lung injury. Thus, these results provide evidence that A18 could be used as a broad-spectrum antiviral and may contribute to the development of novel therapeutic targets to control these viral infections and pathogenesis.

Impact of Penicillin Allergy Label on Clinical Outcomes of Pneumonia in Children.

BACKGROUND: Penicillin (PCN) allergy label, reported in approximately 5% of children, influences antibiotic choice and prolongs hospital stay. To our knowledge, the impact of PCN allergy label on clinical outcomes of pneumonia in children is not well characterized. OBJECTIVES: To investigate the impact of PCN allergy label on clinical outcomes of pneumonia in children. METHODS: In this propensity score-matched cohort study, we used the TriNetX research network, a population-based database, to compare the 30-day risk of hospitalization, need for intensive level of care, and acute respiratory failure from pneumonia between pediatric patients (aged 1-17 years) with and without a PCN allergy label after matching the 2 cohorts for demographic and medical comorbidities. Antibiotic prescription patterns were also contrasted. RESULTS: When comparing 3793 pediatric patients with pneumonia labeled with a PCN allergy with matched children without a PCN allergy label, PCN allergy label was associated with a higher risk of hospitalization (relative risk [RR], 1.15; 95% confidence interval [CI], 1.07-1.23), acute respiratory failure (RR, 1.27; 95% CI, 1.17-1.39), and need for intensive level of care (RR, 1.46; 95% CI, 1.15-1.84). PCN allergy label resulted in overutilization of broader-spectrum antibiotics and increased complications including cutaneous drug reactions (RR, 2.43; 95% CI, 1.31-4.52) and Clostridioides difficile infection (RR, 2.25; 95% CI, 1.14-4.44). CONCLUSION: Children with a PCN allergy label are more likely to be hospitalized, receive broader-spectrum antibiotics, and develop acute respiratory failure from pneumonia. Delabeling may offer a way to lessen morbidity from pneumonia in children.

A New Bacteriocin from Latilactobacillus sakei: In vitro and In situ Application.

AIMS AND BACKGROUND: Natural preservatives are a viable alternative to replace chemical preservatives that have potential toxicity and carcinogenic effects. OBJECTIVE: To prove the effectiveness in increasing the microbiological stability of Minas Frescal cheese with the addition of a bacteriocin obtained from Latilactobacillus sakei as a natural preservative. METHODS: A new broad-spectrum bacteriocin was evaluated for its functional activity in vitro and in situ when applied in the formulation of Minas Frescal cheese. A commercial bacteriocin was used as a positive control. RESULTS: The inhibitory action of the bacteriocin studied was confirmed, with a reduction of 42.86% in the count of coagulase-positive Staphylococcus in relation to the negative control, at the end of the 30 days of study. For the group of thermotolerant coliforms, the bacteriocin studied showed greater efficiency than the commercial preservative. In vitro analyzes showed the inhibitory action of bacteriocin, above 87% inhibition against S. aureus, E. coli and Salmonela enteritidis, and approximately 90% against Listeria monocytogenes. CONCLUSION: It was concluded that the bacteriocin produced by the Latilactobacillus sakei strain has great potential for application in foods such as Minas Frescal cheese.

Honokiol and Alpha-Mangostin Inhibit Mayaro Virus Replication through Different Mechanisms.

Mayaro virus (MAYV) is an emerging arbovirus with an increasing circulation across the Americas. In the present study, we evaluated the potential antiviral activity of the following natural compounds against MAYV and other arboviruses: Sanguinarine, (R)-Shikonin, Fisetin, Honokiol, Tanshinone IIA, and α-Mangostin. Sanguinarine and Shikonin showed significant cytotoxicity, whereas Fisetin, Honokiol, Tanshinone IIA, and α-Mangostin were well tolerated in all the cell lines tested. Honokiol and α-Mangostin treatment protected Vero-E6 cells against MAYV-induced damage and resulted in a dose-dependent reduction in viral progeny yields for each of the MAYV strains and human cell lines assessed. These compounds also reduced MAYV viral RNA replication in HeLa cells. In addition, Honokiol and α-Mangostin disrupted MAYV infection at different stages of the virus life cycle. Moreover, Honokiol and α-Mangostin decreased Una, Chikungunya, and Zika viral titers and downmodulated the expression of E1 and nsP1 viral proteins from MAYV, Una, and Chikungunya. Finally, in Honokiol- and α-Mangostin-treated HeLa cells, we observed an upregulation in the expression of type I interferon and specific interferon-stimulated genes, including IFNα, IFNß, MxA, ISG15, OAS2, MDA-5, TNFα, and IL-1ß, which may promote an antiviral cellular state. Our results indicate that Honokiol and α-Mangostin present potential broad-spectrum activity against different arboviruses through different mechanisms.

The Banana MaWRKY18, MaWRKY45, MaWRKY60 and MaWRKY70 Genes Encode Functional Transcription Factors and Display Differential Expression in Response to Defense Phytohormones.

WRKY transcription factors (TFs) play key roles in plant defense responses through phytohormone signaling pathways. However, their functions in tropical fruit crops, especially in banana, remain largely unknown. Several WRKY genes from the model plants rice (OsWRKY45) and Arabidopsis (AtWRKY18, AtWRKY60, AtWRKY70) have shown to be attractive TFs for engineering disease resistance. In this study, we isolated four banana cDNAs (MaWRKY18, MaWRKY45, MaWRKY60, and MaWRKY70) with homology to these rice and ArabidopsisWRKY genes. The MaWRKY cDNAs were isolated from the wild banana Musa acuminata ssp. malaccensis, which is resistant to several diseases of this crop and is a progenitor of most banana cultivars. The deduced amino acid sequences of the four MaWRKY cDNAs revealed the presence of the conserved WRKY domain of ~60 amino acids and a zinc-finger motif at the N-terminus. Based on the number of WRKY repeats and the structure of the zinc-finger motif, MaWRKY18 and MaWRKY60 belong to group II of WRKY TFs, while MaWRKY45 and MaWRKY70 are members of group III. Their corresponding proteins were located in the nuclei of onion epidermal cells and were shown to be functional TFs in yeast cells. Moreover, expression analyses revealed that the majority of these MaWRKY genes were upregulated by salicylic acid (SA) or methyl jasmonate (MeJA) phytohormones, although the expression levels were relatively higher with MeJA treatment. The fact that most of these banana WRKY genes were upregulated by SA or MeJA, which are involved in systemic acquired resistance (SAR) or induced systemic resistance (ISR), respectively, make them interesting candidates for bioengineering broad-spectrum resistance in this crop.

Characterization and Differential Cytotoxicity of Gramicidin Nanoparticles Combined with Cationic Polymer or Lipid Bilayer.

Gramicidin (Gr) nanoparticles (NPs) and poly (diallyl dimethyl ammonium) chloride (PDDA) water dispersions were characterized and evaluated against Gram-positive and Gram-negative bacteria and fungus. Dynamic light scattering for sizing, zeta potential analysis, polydispersity, and colloidal stability over time characterized Gr NPs/PDDA dispersions, and plating and colony-forming units counting determined their microbicidal activity. Cell viabilities of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans in the presence of the combinations were reduced by 6, 7, and 7 logs, respectively, at 10 µM Gr/10 µg·mL-1 PDDA, 0.5 µM Gr/0. 5µg·mL-1 PDDA, and 0.5 µM Gr/0.5 µg·mL-1 PDDA, respectively. In comparison to individual Gr doses, the combinations reduced doses by half (S. aureus) and a quarter (C. albicans); in comparison to individual PDDA doses, the combinations reduced doses by 6 times (P. aeruginosa) and 10 times (C. albicans). Gr in supported or free cationic lipid bilayers reduced Gr activity against S. aureus due to reduced Gr access to the pathogen. Facile Gr NPs/PDDA disassembly favored access of each agent to the pathogen: PDDA suctioned the pathogen cell wall facilitating Gr insertion in the pathogen cell membrane. Gr NPs/PDDA differential cytotoxicity suggested the possibility of novel systemic uses for the combination.

Synthesis and Evaluation of the Antifungal and Toxicological Activity of Nitrofuran Derivatives.

Fungal diseases affect more than 1 billion people worldwide. The constant global changes, the advent of new pandemics, and chronic diseases favor the diffusion of fungal pathogens such as Candida, Cryptococcus, Aspergillus, Trichophyton, Histoplasma capsulatum, and Paracoccidioides brasiliensis. In this work, a series of nitrofuran derivatives were synthesized and tested against different fungal species; most of them showed inhibitory activity, fungicide, and fungistatic profile. The minimal inhibitory concentration (MIC90) values for the most potent compounds range from 0.48 µg/mL against H. capsulatum (compound 11) and P. brasiliensis (compounds 3 and 9) to 0.98 µg/mL against Trichophyton rubrum and T. mentagrophytes (compounds 8, 9, 12, 13 and 8, 12, 13, respectively), and 3.9 µg/mL against Candida and Cryptococcus neoformans strains (compounds 1 and 5, respectively). In addition, all compounds showed low toxicity when tested in vitro on lung cell lines (A549 and MRC-5) and in vivo in Caenorhabditis elegans larvae. Many of them showed high selectivity index values. Thus, these studied nitrofuran derivatives proved to be potent against different fungal species, characterized by low toxicity and high selectivity; for these reasons, they may become promising compounds for the treatment of mycoses.

Characterization and survival of broad-spectrum biocontrol agents against phytopathogenic fungi.

The current study intended to isolate, characterize and identify biocontrol bacteria possessing broad-spectrum antifungal activity from the phyllosphere of different crops including maize, wheat and potato and to assess their growth-promoting activity. In this study 14/113 biocontrol bacteria showed antifungal activity. Bacterial isolates M11 and M33 from maize out of 113 were re-selected on the basis of their strong (more than 50%) broad spectrum antifungal activity after their assessment against four economically important phytopathogenic fungi including Alternaria alternata, Rhizoctonia solani, Fusarium oxysporum and Fusarium verticillioides. The isolates were further assessed for plant growth promoting traits, i.e., indole-3-acetic acid production, phosphate solubilization, production of cellulase, microbial volatile compounds, hydrogen cyanide and siderophores. All fourteen isolates showed positive results for the production of indole-3-acetic acid hormone and cellulase enzyme, 10 isolates were positive for hydrogen cyanide production; siderophores production was observed in 7 isolates while 5 isolates showed ability to solubilize inorganic phosphate. Microbial volatile compounds were only synthesized by M11 and M33, which were identified as Bacillus amyloliquefaciens and Bacillus subtilis respectively by 16S rRNA gene sequencing. The survival study revealed that biocontrol bacteria B. amyloliquefaciens and B. subtilis have the ability to survive in cost effective molasses containing carrier material up to a three-month period.

RXam2, a NLR from cassava (Manihot esculenta) contributes partially to the quantitative resistance to Xanthomonas phaseoli pv. manihotis.

KEY MESSAGE: The overexpression of RXam2, a cassava NLR (nucleotide-binding leucine-rich repeat) gene, by stable transformation and gene expression induction mediated by dTALEs, reduce cassava bacterial blight symptoms. Cassava (Manihot esculenta) is a tropical root crop affected by different pathogens including Xanthomonas phaseoli pv. manihotis (Xpm), the causal agent of cassava bacterial blight (CBB). Previous studies have reported resistance to CBB as a quantitative and polygenic character. This study sought to validate the functional role of a NLR (nucleotide-binding leucine-rich repeat) associated with a QTL to Xpm strain CIO151 called RXam2. Transgenic cassava plants overexpressing RXam2 were generated and analyzed. Plants overexpressing RXam2 showed a reduction in bacterial growth to Xpm strains CIO151, 232 and 226. In addition, designer TALEs (dTALEs) were developed to specifically bind to the RXam2 promoter region. The Xpm strain transformed with dTALEs allowed the induction of the RXam2 gene expression after inoculation in cassava plants and was associated with a diminution in CBB symptoms. These findings suggest that RXam2 contributes to the understanding of the molecular basis of quantitative disease resistance.

Antibiotic Use in Neonatal Intensive Care Units in China: A Multicenter Cohort Study.

OBJECTIVE: To provide national-level antibiotic use data from Chinese neonatal intensive care units to inform future antimicrobial stewardship using a large contemporary cohort of preterm infants in China. STUDY DESIGN: This retrospective cohort study enrolled all infants less than 340/7 weeks of gestation admitted to 25 tertiary neonatal intensive care units across China between May 1, 2015, and April 30, 2018. The antibiotic use rate (AUR) was defined as the number of days an infant was prescribed with 1 or more antibiotics divided by the total length of hospital stay. RESULTS: Among 24 597 eligible infants, 21 736 (88.4%) infants received antibiotics. The median AUR was 441 per 1000 patient-days (IQR, 242-692 per 1000 patient-days). The median duration of each antibiotic course was 9 days (IQR, 6-14 days). Overall, 64.6% infants received broad-spectrum antibiotics, with a median broad-spectrum AUR of 250 per 1000 patient-days (IQR, 0-500 per 1000 patient-days), accounting for 70.7% of all antibiotic use days. Overall, 68.7% of all antibiotic use occurred among infants without infection-related morbidities, with a median duration of 8 days (IQR, 6-13 days) for each course. Only 22.9% episodes of culture-negative sepsis were prescribed with antibiotics for 7 or fewer days, and 34.7% were treated with antibiotics for more than 14 days. For early antibiotic use, the median duration of antibiotic therapy within 7 days after birth was 7 days (IQR, 4-7 days). CONCLUSIONS: A high AUR among infants without infections, prolonged antibiotic durations, and excessive use of broad-spectrum antibiotics were the main problems of antibiotic use in Chinese neonatal intensive care units and should be high-impact focuses for future stewardship interventions.

From field to plate: Agricultural pesticide presence in the guayas estuary (Ecuador) and commercial mangrove crabs.

Mangroves are unique coastal ecosystems, located in tropical and subtropical regions. Yet, the functioning of these essential ecosystems is threatened by the presence of pollutants, including pesticides originating from agricultural activities. We investigated pesticide residues in the Guayas estuarine environment, since agricultural activities rapidly increased in the Guayas river basin over the past decades. A multi-residue analysis involving a selection of 88 pesticides was performed on the white meat and the hepatopancreas of the red mangrove crab (Ucides Occidentalis) at 15 sampling sites within the Guayas estuary along with water, sediment, and leaves samples. We found that 35 active compounds were present in the Guayas estuary, of which pyrimethanil was most commonly detected and had the highest concentrations in almost all compartments. Also, cadusafos was present in all studied compartments of the Guayas mangrove system and several prohibited pesticides (including carbendazim, carbofuran, and parathion) were detected. An ecotoxicological and probabilistic consumer risk assessment pointed out that current butachlor, carbendazim, and fludioxonil concentrations can cause adverse effects in aquatic organisms in the long term. Moreover, high potential acute and chronic risks of cadusafos residues on aquatic invertebrates and of diuron on algae in the Guayas wetlands were observed. Still, the exposure results indicated that the health risk for the consumers of the commercial red mangrove crab is low concerning cadusafos, chlorpyrifos, diuron, linuron, and pyrimethanil residues in crab tissues. The findings presented in this research can provide a useful basis for local water managers and environmental conservation groups to act and reduce the usage of pesticides, to avoid threatening aquatic and human health.

Relevant Features of Polypharmacologic Human-Target Antimicrobials Discovered by Machine-Learning Techniques.

Polypharmacologic human-targeted antimicrobials (polyHAM) are potentially useful in the treatment of complex human diseases where the microbiome is important (e.g., diabetes, hypertension). We previously reported a machine-learning approach to identify polyHAM from FDA-approved human targeted drugs using a heterologous approach (training with peptides and non-peptide compounds). Here we discover that polyHAM are more likely to be found among antimicrobials displaying a broad-spectrum antibiotic activity and that topological, but not chemical features, are most informative to classify this activity. A heterologous machine-learning approach was trained with broad-spectrum antimicrobials and tested with human metabolites; these metabolites were labeled as antimicrobials or non-antimicrobials based on a naïve text-mining approach. Human metabolites are not commonly recognized as antimicrobials yet circulate in the human body where microbes are found and our heterologous model was able to classify those with antimicrobial activity. These results provide the basis to develop applications aimed to design human diets that purposely alter metabolic compounds proportions as a way to control human microbiome.

Hemivulvectomía radical por gangrena de fournier en mujer con antecedente de radioterapia pélvica / Radical hemivulvectomy due to Fournier's gangrene in a woman with a history of pelvic radiotherapy

RESUMEN La Gangrena de Fournier es una infección necrotizante que afecta al área genitourinaria, perineal y perianal. Se trata de una infección muy grave con una rápida evolución a estadios avanzados y una elevada tasa de morbimortalidad asociada. Sin embargo, con frecuencia tiende a ser infradiagnosticada. Es vital en su manejo un diagnóstico basado en la sospecha clínica e inicio del tratamiento quirúrgico precoz con desbridamiento y exéresis de los tejidos afectos. Además, es crucial la asociación de antibioterapia de amplio espectro y el apoyo nutricional de soporte en el pronóstico de dicha entidad. En este artículo se revisa un caso clínico de Gangrena de Fournier, en una paciente con antecedentes de osteítis púbica y cistitis derivadas del tratamiento mediante radioterapia pélvica, diagnosticado y tratado con una hemivulvectomía radical, antibioterapia y lavados quirúrgicos en nuestro Hospital.

ABSTRACT The Fournier's Gangrene is a necrotizing infection which is located in the perineal area. It´s a severe infection, which involves a quick evolution to advanced stages where a high morbimortality rate is associated. However, it often tends to be underdiagnosed in early stages. The most important in the diagnosis is a high clinical suspicion and subsequent surgical treatment which is base on a desbridalment and exeresis of the affected tissues. In addition, the association of broad-spectrum antibiotic therapy and nutritional support are crucial. This report reviews a clinical case of Fournier's Gangrene, in a patient with a history of radiation induced cystitis and pubic osteitis after pelvic radiotherapy, diagnosed and treated with a radical hemivulvectomy, antibiotic therapy and lavages in our Hospital.